Pediatric vascular anomalies with airway compromise

Abstract Vascular anomalies are rare lesions of diverse nature that may affect the head and neck region. Any mass in or around the upper airway has the potential to obstruct or compromise it. The absolute priority, before etiologic treatment, is the evaluation of the risk for the airway and its management. Prenatal diagnosis of an upper airway obstruction requires a planned delivery in a center having a specialized team experienced in managing a compromised feto‐neonatal airway, and who could perform an ex‐utero intrapartum treatment to secure the airway. Even after birth, the airway remains central in the patient's overall management. Signs and symptoms of airway compromise must be evaluated keeping in mind the specific requirements of infants and small children and being aware that rapid worsening may occur. The treatment is then tailored to the patient and his lesion with the goal of improving symptoms while avoiding treatment‐related complications. Maintaining reasonable expectations by the patient and families are part of a successful management. Cure is achievable for small and localized lesions, but symptom relief and mitigation of functional, esthetic and psychological impairments is the goal for large and complex lesions. If a tracheotomy was required, decannulation is one of the primary management goals.


| INTRODUCTION
The term vascular anomaly describes a wide spectrum of lesions composed of vascular tumors and vascular malformations. 1,2 The widely accepted classification by the international society for the study of vascular anomalies (ISSVA) 1,3 excludes terms like "lymphangioma", "cystic hygroma" and "arterio-venous hemangioma". The suffix "angioma" is now strictly restricted to vascular tumors histologically displaying increased cell proliferation. This classification eventually solved the confusion around this spectrum of pathologies. 3 Both vascular tumors and vascular malformations can affect the head and neck region with potential functional and aesthetic impairments. Symptoms depend on the nature, size and the localization of the lesions and include airway compromise, obstructive sleep apnea, dysphagia, sialorrhea, impaired mastication, abnormal speech intelligibility, and facial deformities. 4 When the buccal cavity, pharynx, larynx, trachea and mediastinum are affected, management of airway compromise is the priority before definitive treatment of the vascular anomaly itself.
The airway must be secured if it is obstructed and protected from potential future obstruction to prevent any emergent situation.
Indeed, symptoms can rapidly deteriorate with vascular anomaly growth or swelling in case of infection, trauma, intralesional bleeding and hormonal changes 5 or as a result of the treatment itself. 4 Ranging from unnoticeable to massive, perinatal and pediatric vascular anomalies with airway compromise represent a clinical challenge and requires timely management in specialized centers having multidisciplinary teams with experience in managing a difficult pediatric airway. The primary goal of the management is obtaining a "safe" airway that would then permit a case-specific treatment. Beyond the life-threatening airway obstruction, management may also deal with impaired oral feeding, orthognathic considerations, speaking skills and decannulation programs. Therefore, depending on the type of lesion and its extent, treatment goals may vary from complete remission to improvement of function and quality of life, while minimizing treatment-related complications. The quality of the noise provides clues to the location of the airway obstruction while its intensity correlates, to a certain extent, with the degree of obstruction. 6 An obstruction at the level of the larynx or trachea usually produces a high-pitched sound, called stridor, which can be inspiratory (supraglottic), biphasic (glottic/subglottic) or expiratory (trachea). An obstruction at the level of the pharynx or the oral cavity produces more of a low pitch noise, analog to snoring, usually inspiratory, and is called stertor. 6 Depending on the location of the vascular anomaly, the degree of obstruction can worsen in a supine position, for example with lesions involving the base of the tongue. Feeding difficulty and failure to thrive is also an indicator of the severity of the airway obstruction.
The nature of the lesion (compressible or not), together with its localization (endoluminal or extraluminal) has important implications in the perinatal and post-natal management of the compromised airway. As a general principle, in experienced centers, tracheotomy should be avoided or delayed as much as possible to prevent any further tracheal damage and to avoid tracheotomy-related impairements. [6][7][8] Noninvasive ventilation and/or tracheal intubation can temporarily secure a compromised airway while providing time to relieve an obstruction, for example with decompressive aspiration or early surgery. Complex and/or multilevel lesions obstructing the upper airway are difficult to treat and are best addressed under a tracheotomy-secured airway. Performing a tracheotomy in case of a large vascular anomaly of the neck can itself be challenging. In any case, the tracheotomy should always be performed with the airway secured by either a tracheal intubation or rigid bronchoscopy. Surgical technique, multidisciplinary care, parents support and correct decannulation protocols are then crucial to minimize tracheotomy-related complications and impairements. 6,9 Decannulation then becomes one of the primary goals of treatment.

| AIRWAY MANAGEMENT IN VASCULAR ANOMALIES DIAGNOSED IN UTERO
Progresses made in prenatal screening with ultrasound (US) and magnetic resonance imaging (MRI) allow in utero detection of fetal head and neck masses with potential airway compromise. 10,11 Even if the diagnosis can be inaccurate, 12 any suspicion should evoke a multidisciplinary evaluation to plan a safe perinatal airway management, sometimes with an ex-utero intrapartum treatment (EXIT) procedure.
An EXIT procedure provides up to 90 minutes to access the airway under utero-placental circulation, but these require highly trained teams 13 and may put the mother at risk of complications including severe uterine hemorrhage. 14 Congenital high airway obstruction syndrome (CHAOS), which has specific signs 15 such as polyhydramnios and inverted diaphragm, is the only true intrauterine upper airway obstruction. Fetal neck masses responsible for a CHAOS always require an EXIT procedure to secure the airway before any consideration of etiologic treatment. Lymphatic malformation (LM) is the most frequent neck mass diagnosed in utero, followed by teratoma. 16 An EXIT procedure should be restricted to selected cases to avoid unnecessary maternal and fetal risks. 17 Because most vascular anomalies are soft and/or compressible, CHAOS is unlikely, and most patients can be intubated through laryngoscopy or rigid bronchoscopy at birth. In a series of 112 fetuses with prenatal diagnosis of cervical LM, 13 (11%) were delivered through an EXIT procedure. 17 The criteria to perform an EXIT procedure were deviation, compression or obstruction of the airway and involvement of the floor of mouth and tongue. Of those 13 fetuses, 11 could be intubated with laryngoscopy (7) or rigid bronchoscopy (4), 1 required a tracheotomy, and one with a massive involvement of the face and neck died after parental refusal of a tracheotomy. 17 The authors conclude that EXIT procedure remains the gold standard, in specialized centers, to address prenatal LM with high suspicion of airway compromise. 17

| Vascular tumors
The list of vascular tumors is large, 3 and includes infantile hemangioma (IH), congenital hemangioma, kaposiform hemangioendothelioma and pyogenic granuloma. Because of space constraints, this review will only discuss IH, the most frequent vascular tumor impacting the airway.

| Infantile hemangioma (IH)
IH is the most frequent tumor of infancy affecting up to 5% of children, 18 60% of which in the head and neck region, 19 with a 2-3:1 female predominance. 3,6 IH can impact the airway when located in the oral cavity, pharynx or larynx. The subglottic localization of IH, termed subglottic hemangioma (SGH), represents 1.5% of congenital anomalies of the larynx 6,20 and is classically linked to segmental cutaneous IH, especially with a bilateral beard distribution (association 10-30%). [21][22][23] Although only 1-2% of patients with cutaneous IH have a silent SGH, it is prudent to look for it before patients present with a critical airway. 30% of beard distributed IH have a PHACE syndrome (Posterior fossa anomalies, Hemangioma, Arterial lesions, Cardiac abnormalities/aortic coarctation, and Eye abnormalities), these patients should be thoroughly investigated. 24 Early diagnosis should prevent high rate of repeated hospitalizations (30%) and mortality (2%) described before the use of Propranolol. 23,25 However, up to 55% of subglottic hemangiomas present as recurrent/persistent/ severe croup without skin lesions, 26 often leading to a delayed diagnosis. The typical clinical course of IH is a proliferative phase during the first months of life reaching its maximal size around 9-12 months, followed by a spontaneous involution by 24-30 months. 27,28 The mean age of diagnosis of an airway IH is around 3.6 months. 29 A subglottic hemangioma can be suspected on awake fiberoptic laryngoscopy and confirmed with angio-CT as an intensely contrastenhancing, lobular, well delimited mass. 21 MRI is also diagnostic with the advantage of avoiding infant irradiation but it often requires a sedation. 21 With the disadvantages of a general anesthesia for subglottic hemangioma that are now essentially treated medically, direct laryngoscopy is usually diagnostic, and it provides the opportunity to precisely assess the risk for a critical airway. On rod lens endoscopy, subglottic hemangioma presents as smooth submucosal, compressible, pink or blue mass with surface telangiectasias. Biopsy is often not necessary but positive GLUT1 staining confirms the diagnosis. 3 A subglottic hemangioma is a time bound self-limiting vascular tumor that involutes by the 3rd birthday of the child. Therefore, the treatment should be directed towards securing and maintaining a safe airway and avoiding sequelae of the treatment. Historically, treatment options were: tracheotomy followed by wait-&-watch policy until spontaneous involution occurs followed by decannulation 30 ; laser (CO 2 31 or KTP 32 ) ablation, endoscopic microdebrider, 33 intra-lesional and systemic steroids and open neck surgery. 34,35 Open surgical resection offers a high degree of success, with more than 90% patients remaining symptom-free from their subglottic lesion, not requiring a tracheotomy when primarily employed as a single-staged technique. 35 Since the initial report in 2008, 36

| Lymphatic malformations
With a reported incidence of 1.2 to 2.8 per 1000 42 live-births, LMs are the most frequent lesion with potential airway compromise diagnosed on prenatal screening. 43 Always present at birth, although not always obvious, LMs grow proportionally to the patient with episodes of swelling/remission linked to infection, and trauma. 44 Only around 60% of LMs are evident at birth and 80%-90% are diagnosed by the ae of two. 45 They exist in any body location but the head and neck is most frequently affected, with up to 73% of upper aerodigestive tract involvement. 44 In a retrospective series of 141 patients with upper aerodigestive tract LM, the buccal cavity was affected in 75%, the oropharynx in 36%, the hypopharynx in 6%, the parapharynx in 30%, and the retropharnyx in 9%. 44 The supraglottis was only involved in case of large LM involving other subsites, most frequently the buccal cavity and/or pharynx. There were no involvement of the glottis and subglottis. 44 All these localizations can result in airway obstruction, especially when the lesion is in direct contact with the airway. 46  Microcysts are known to be more invasive to surrounding structure, harder to treat and more prone to recurrences/persistent disease. 48 After birth, the diagnosis is suspected on clinical exam and confirmed with US or/and MRI. Biopsy is often not necessary but can confirm the diagnosis. 48  swelling, is also an efficient option in such cases. 55 Large/diffuse mucosal lesions are better addressed with the airway protected by a tracheotomy. In these cases the treatment is multimodal (medical treatment, surgery, sclerotherapy, targeted therapy) with the goal of relieving symptoms while minimizing treatment-induced complications. 56 Multiple sclerosing agents can be used and sclerotherapy has shown good efficacy but with some complications. 57 Much care must be taken when planning sclerotherapy in a VM close to the airway as these lesions are known to swell more than LMs after sclerotherapy. Surgery is a good alternative for small well defined lesions (through excision) and large VMs in close proximity to a critical structure (by debulking) and should be favored if crucial structures are involved or as part of the multimodal treatment. 41  however, many lesions will require long and multimodal treatments with a tracheotomy securing the airway. In these cases, decannulation becomes one major goal of the treatment. The complex and various nature of vascular tumors and anomalies requires treatment selection to be tailored to the individual patient according to the disease characteristics and the functional consequences. Recurrence and incomplete treatment are common, but timely management by multidisciplinary team approach is key to the best possible outcomes.

ACKNOWLEDGMENTS
Open access funding provided by Universite de Lausanne.

CONFLICT OF INTEREST
None.

DATA AVAILABILITY STATEMENT
The data is available on request from the authors (The data that support the findings of this study are available from the corresponding author upon reasonable request.)